Risk factors for onset and persistence of TMD: Myogenous temporomandibular disorder (TMD), with or without arthralgia, ranks second only to headache as the clinical condition most likely to cause craniofacial pain and dysfunction in the U.S. population. During the last decade, a small number of epidemiological studies have attempted to quantify the incidence of TMD in populations of European heritage;however, no investigative team to date has undertaken a large-scale, hypothesis-driven, prospective study designed to identify biopsychosocial and genetic risk factors for the onset and persistence of this vexing pain disorder. We propose to conduct a comprehensive, prospective cohort study of the incidence of TMD in collaboration with an internationally recognized group of epidemiologists, pain researchers, and geneticists. Participants will be enrolled and followed prospectively at four research institutions and by our Data Coordinating Center (Battelle Memorial Institute). Our three goals are to: a) undertake a five-year, prospective cohort study of 3200 initially TMD-free individuals recruited from major ethnic and racial strata at four study sites, quantifying incidence rates of first-onset-TMD;b) undertake a case-control study by recruiting 200 people with chronically symptomatic TMD identified during cohort recruitment whose history of TMD precludes them from the prospective study;c) to identify in both groups the individual and joint effects of predictors of TMD risk using a conceptual, causal model for TMD that we have developed based our own studies and other published research. Our preliminary epidemiological findings have led to the central hypothesis that pain amplification and psychological factors, both of which are influenced by genetic variants, represent causal risk factors that influence TMD onset and persistence. The outcomes of our proposed study will identify the primary socio-demographic, clinical, biological, psychological, and genetic risk factors for TMD onset and persistence. In so doing, we will obtain important and novel information regarding the etiopathogenesis of TMD, which will assist with the development of evidenced based pharmacological and behavioral interventions for TMD.